Hypoprothrombinemia Associated With Cefoperazone Therapy

Cefoperazone, a beta-lactam antibiotic with a methylthiotetrazole side chain, has been reported infrequently to cause hypoprothrombinemia and hemorrhage. We retrospectively analyzed the records of 80 patients who had been given this drug for more than 72 hours. Nine patients received vitamin K1 (phytonadione) prophylaxis and had no evidence of hemorrhage. Of the remaining 71 patients, 32 had prothrombin times measured; 14 of them had hypoprothrombinemia. Prothrombin times ranged from 14.8 to 97.3 seconds at a mean of 6.2 days after initiation of therapy. Seven of the 14 patients had clinically significant hemorrhage and five required transfusions. Two patients with clinically evident hemorrhage died during or immediately after cefoperazone therapy. Prothrombin times rapidly returned to normal in all patients treated with phytonadione. We believe hypoprothrombinemia is a more common complication of cefoperazone therapy than is generally acknowledged, and is preventable. Unless clinically contraindicated, we recommend that all patients treated with cefoperazone receive phytonadione prophylaxis.